Is Roxithromycin Better than Amoxicillin in the Treatment of Acute Lower Respiratory Tract Infections in Primary Care?

Compliance with the medication regimen was high. Data from electronic monitoring were available for 160 patients (78 in the amoxicillin group, 82 in the roxithromycin group). The overall compliance rate for patients in both groups (ie, the number of doses taken divided by the number of doses prescribed) was 98%. In the amoxicillin group, the numbers of patients with less than 90% compliance in taking the tablets and capsules were 7 and 4, respectively. In the roxithromycin group, compliance in taking the tablets was at least 90% in all patients but compliance in taking the capsules was less than 90% in 6 patients.

Discussion

This community-based study shows that amoxicillin and roxithromycin are equally effective in the treatment of LRTI in the Netherlands. Clinical cure rates after 10 days of antibiotic treatment were approximately 90% in both study groups, although complete absence of symptoms was achieved in only a minority of cases. After 28 days of follow-up, cure rates remained high. The amoxicillin group had a significantly higher cure rate than the roxithromycin group as evidenced by the decrease in symptoms. However, this significant difference in favor of the amoxicillin group did not alter the PCPs’ overall conclusion after complete follow-up: that 90% of patients who received either drug had been effectively treated. Patients’ diary entries agreed with that impression.

The time to resolution of symptoms, the cumulative cure rate per day, and the influence of the illness on daily activities were not significantly different between patients treated with amoxicillin versus those given roxithromycin. Adverse events were mild and were divided evenly over both groups with the exception of diarrhea, which occurred more often in those taking amoxicillin.

In our study, complete absence of symptoms and signs after 28 days, as assessed by both physicians and patients, was achieved in only approximately half the patients. Complete remission of LRTI often takes more than 4 weeks.

Although LRTI is often managed in primary care, diagnostic and therapeutic decisions are usually based on the experiences of hospital-based specialists and on the results of trials conducted in hospital settings. Generalizing these results to primary care is of limited value, since disease in patients recruited for these studies is often at a later stage and more serious. In our trial, patients were recruited, diagnosed, and treated by PCPs in their natural setting, maintaining regular care as much as possible.

Nevertheless, generalization of our findings to everyday care may not be valid. To explore the degree of selection in our recruited patients, we compared the actual numbers of cases of LRTI in 3 practices (with a total of 9 PCPs and a total population of 13,269) with the numbers included in the present trial during 1 year of the inclusion period. Of the 463 presumably eligible patients, only 43 (9%) were actually included. This proportion is similar to that in a recent study of randomized controlled trials in primary care in which less than 10% of the eligible population were recruited for the trial.³¹ Included patients did not differ from other eligible patients with regard to age, clinical diagnosis, severity of illness, and need for antibiotic treatment (according to the PCPs).

Clinical studies, mostly in inpatient settings, on community-acquired pneumonia have identified causative pathogens in 50% to 69% of patients.^{14-17,21,23,32,33} Outpatient studies of acute bronchitis and LRTI have generally reported considerably lower percentages (16% to 44%).^19,20,34-36 In our study, pathogens that presumably caused LRTI were found in 46% of patients.

Because atypical pathogens were the presumptive causative agent in only 3 cases (2 M pneumoniae, 1 L pneumophila), the potential advantage of macrolide antibiotics over amoxicillin is minimal. Furthermore, bacterial resistance to macrolide antibiotics is believed to be considerable.^37,38 In Finland, bacterial resistance to erythromycin has been shown to rise quickly after an increase in the consumption of macrolide antibiotics.³⁹ In contrast to alarming reports in the literature,^{14,17,22,40,41} the low incidence of M pneumoniae and L pneumophila found in the current study supports the conservative approach (ie, amoxicillin or doxycycline) to treating community-acquired LRTI in the Netherlands.

M pneumoniae occurs at high rates in 4-year to 5-year cycles.⁴² This timing implies that the frequency of M pneumoniae might be higher if the same study were performed 1 year later. Because most M pneumoniae infections are self-limiting and clinical cure rates of macrolide antibiotics compared with those of placebo are the same,^43,44 however, this epidemiologic observation does not change the conclusions of the present study.

Compliance with medication was reliably measured and quantified by Medical Event Monitoring Systems. For both ethical and practical reasons, patients were informed about the monitoring mechanism. Their knowledge about the monitoring may have slightly increased compliance as compared with daily practice, although this assumption has not been confirmed in other studies.^45,46 Furthermore, compliance with antibiotic regimens is known to be greater than compliance with chronic medication regimens.^47,48